We have discovered that TF is not mere assay artifact; we show that TF is derived from antigen-specific CD8+ memory T-cells, acts upon APCs to induce IL-6, and subsequently stimulates memory Tc17 activity to enhance responses in mucosal challenge models for both mice and humans. We obtained partial sequencing of TF, with analytical chemistry evidence suggesting a hybrid molecule of S100 peptides, antigen-binding regions, and nucleic acids. While numerous questions remain around the structure, genesis, and receptor of TF, our findings suggest the time for a renewal of research into the therapeutic potential of transfer factor is long overdue.